title: Positive inotropic activity induced by a dehydroisoandrosterone derivative in isolated rat heart model.
abstract: Experimental studies indicate that some steroid derivatives have inotropic activity; nevertheless, there is scarce information about the effects of the dehydroisoandrosterone and its derivatives at cardiovascular level. In addition, to date the cellular site and mechanism of action of dehydroisoandrosterone at cardiovascular level is very confusing. In order, to clarify those phenomena in this study, a dehydroisoandrosterone derivative was synthesized with the objective of to evaluate its activity on perfusion pressure and coronary resistance and compare this phenomenon with the effect exerted by dehydroisoandrosterone. The Langendorff technique was used to measure changes on perfusion pressure and coronary resistance in an isolated rat heart model in absence or presence of dehydroisoandrosterone and its derivative. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by dehydroisoandrosterone derivative was evaluated by measuring left ventricular pressure in absence or presence of following compounds; flutamide, prazosin, metoprolol and nifedipine. The results showed that dehydroisoandrosterone derivative significantly increased the perfusion pressure and coronary resistance in comparison with the control conditions and dehydroisoandrosterone. Additionally, other data indicate that dehydroisoandrosterone derivative increase left ventricular pressure in a dose-dependent manner [1 × 10(-9)-1 × 10(-4) mmol]; nevertheless, this phenomenon was significantly inhibited by nifedipine at a dose of 1 × 10(-6) mmol. In conclusion, these data suggest that dehydroisoandrosterone derivative induces positive inotropic activity through of activation the L-type calcium channel.
authors.affiliation: Laboratory of Pharmaco-Chemistry at the Faculty of Chemical Biological Sciences of the University Autonomic of Campeche, Av. Agustín Melgar s/n, C.P. 24039, Col. Buenavista, CAM, Mexico, lauro_1999@yahoo.com.
authors.forename: L
authors.initials: L
authors.lastname: Figueroa-Valverde
authors.forename: F
authors.initials: F
authors.lastname: Díaz-Cedillo
authors.forename: E
authors.initials: E
authors.lastname: García-Cervera
authors.forename: E
authors.initials: E
authors.lastname: Pool Gómez
authors.forename: M
authors.initials: M
authors.lastname: López-Ramos
authors.forename: M
authors.initials: M
authors.lastname: Rosas-Nexticapa
authors.forename: R
authors.initials: R
authors.lastname: Martinez-Camacho
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005485:Flutamide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D023421:Models, Animal; D009543:Nifedipine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000726:Androgen Antagonists; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; D003687:Dehydroepiandrosterone; D005485:Flutamide; D008790:Metoprolol; D009543:Nifedipine; D011224:Prazosin